Dual NAV1.2/5HT2a inhibitors for treating CNS disorders

Abstract

Compounds of formula I:are disclosed, as are pharmaceutical compositions containing such compounds. Methods of treating neurological or psychiatric disorders in a patient in need are also disclosed. Such disorders include depression, bipolar disorder, pain, schizophrenia, obsessive compulsive disorder, addiction, social disorder, attention deficit hyperactivity disorder, an anxiety disorder, autism, a cognitive impairment, or a neuropsychiatric symptom such as apathy, depression, anxiety, psychosis, aggression, agitation, impulse control disorders, and sleep disorders in neurological disorders such as Alzheimer's and Parkinson's diseases.

The invention claimed is: 
     
       1. A compound of formula I 
       
         
           
           
               
               
           
         
       
       wherein
 Q is piperidine attached to L 1  at a nitrogen, wherein substituents, when present, are selected from the group consisting of halogen, hydroxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and oxo; 
 R A  is selected from the group consisting of (1) an optionally substituted bicyclic carbocycle containing an aromatic 6-membered ring and a non-aromatic 5-membered ring; and (2) an optionally substituted, bicyclic heterocycle selected from the group consisting of a cyclopenta[b]pyridine, a dihydrobenzofuran, a dihydrofuro[3,2-b]pyridine, a cyclopenta[c]pyridine, an indoline, a pyrrolo[3,4-b]pyridine, and an isoindoline; 
 L 1  is —(CH 2 CHR 1 )—, wherein R 1  is hydrogen or methyl; 
 L 2  is —O—; and 
 R B  is an optionally substituted aromatic carbocycle wherein substituents, when present, are selected from the group consisting of halogen, cyano, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )oxaalkyl, —C(═O)NH 2 , and di(C 1 -C 6 )alkylamino. 
 
     
     
       2. A compound according to  claim 1  wherein R A  is an optionally substituted bicyclic carbocycle containing an aromatic 6-membered ring and a non-aromatic 5-membered ring. 
     
     
       3. A compound according to  claim 1  wherein R A  is an optionally substituted bicyclic heterocycle selected from the group consisting of a cyclopenta[b]pyridine, a dihydrobenzofuran, a dihydrofuro[3,2-b]pyridine, a cyclopenta[c]pyridine, an indoline, a pyrrolo[3,4-b]pyridine, and an isoindoline. 
     
     
       4. A compound according to  claim 1  wherein L 1  is —CH 2 CH 2 —. 
     
     
       5. A compound according to  claim 1  wherein R A  is selected from the group consisting of indane, dihydrobenzofuran, 3-methyldihydrobenzofuran, methylindane, haloindane, cyanoindane, and methoxyindane. 
     
     
       6. A compound according to  claim 1  wherein R B  is selected from the group consisting of benzene, halobenzene, methylbenzene, dimethylbenzene, and methoxybenzene. 
     
     
       7. A compound according to  claim 1  wherein the piperidine Q is unsubstituted or is substituted with one or two methyls. 
     
     
       8. A compound according to  claim 1  wherein R A  is indane. 
     
     
       9. A compound according to  claim 1  wherein R B  is halobenzene. 
     
     
       10. A compound according to  claim 1  wherein R B  is dimethylbenzene. 
     
     
       11. A compound according to  claim 1  selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                 
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